Low dose of fire retardant, 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE47), stimulates the proliferation and differentiation of progenitor Leydig cells of male rats during prepuberty. (15th May 2021)

• Record Type: Journal Article
• Authors: Li, Zengqiang; Li, Huitao; Li, Changchang; Yan, Haoni; Ying, Yingfen; Li, Xiaoheng; Zhu, Qiqi; Ge, Ren-shan; Wang, Yiyan
• Is Part Of: Toxicology letters. Volume 342(2021)
• Page Start: 6
• Page End: 19
• Publication Date: 2021-05-15
• Subjects: BDE47 -- Immature leydig cells -- Proliferation -- Luteinizing hormone -- p53 -- p21; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.02.006
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: BDE47 increases serum testosterone levels during prepubertal exposure. BDE47 increases Leydig cell number. BDE47 up-regulates Star and Scarb1 expression in vivo and in vitro. BDE47 up-regulates CCND1 but down-regulates p53 and p21 expression BDE47 increases the phosphorylation of AKT, ERK1/2, and CREB. Abstract: 2, 2′, 4, 4′-Tetrabromodiphenyl ether (BDE47), a flame retardant, is extensively distributed in the food chain. However, whether BDE47 affects Leydig cell development during prepuberty remains unclear. BDE47 was daily gavaged to 21-day-old Sprague-Dawley male rats with 0 (corn oil), 0.1, 0.2, and 0.4 mg/kg for 14 days. BDE47 did not affect the body weight or testis weight of rats. It significantly increased serum testosterone level at 0.4 mg/kg, but decreased luteinizing hormone (LH) level without affecting estradiol level. BDE47 induced Leydig cell hyperplasia (the number of CYP11A1-positive Leydig cells increased), and up-regulated the expression of Scarb1, Star, Hsd11b1, Pcna, and Ccnd1 in the testis. BDE47 significantly reduced p53 and p21 levels but increased CCND1 level. It also markedly increased the phosphorylation of AKT1, AKT2, ERK1/2, and CREB. BDE47 significantly up-regulated the expression of Scarb1, Star, and Hsd11b1 and stimulated androgen production by immature Leydig cells from rats under basal, LH, and 8Br-cAMP stimulated conditions at 100 nM in vitro. In conclusion, BDE47 increased Leydig cell number and up-regulated the expression of Scarb1 and Star, thereby leading to increased testosterone synthesis.